1. Field of the Invention
This invention relates to certain N-alkylaminofluorenecarboxamides and pharmaceutical compositions containing them. It also relates to the use of such compounds in the treatment or prevention of psychotic disorders such as schizophrenia and other central nervous system diseases. The use of the compounds of this invention to the treatment of these disorders is indicated by the ability of the compounds to bind selectively to dopamine receptor subtypes.
2. Description of the Related Art
The therapeutic effect of conventional antipsychotics, known as neuroleptics, is generally believed to be exerted through blockade of dopamine receptors. However, neuroleptics are frequently responsible for undesirable extrapyramidal side effects (EPS) and tardive dyskinesias, which are attributed to blockade of D.sub.2 receptors in the striatal region of the brain. The dopamine D.sub.3 receptor subtype has recently been identified (Sokoloff, P. et al., Nature 1990, 347, 146). Its unique localization in limbic brain areas and its differential recognition of various antipsychotics suggest that the D.sub.3 receptor may play a major role in the etiology of schizophrenia. Selective D.sub.3 antagonists may be effective antipsychotics free from the neurological side effects displayed by conventional neuroleptics.
U.S. Pat. No. 5,395,835 (May 24, 1994) discloses N-aminoalkyl-2-napthamides which have affinity at dopamine D.sub.3 receptors. The novel compounds of Claim 1 of the present invention differ significantly from this prior art in that they possess a fluorenecarboxamide substructure.
Murray, P. J. et al. (A Novel Series of Arylipiperazines with High Affinity and Selectivity for the Dopamine D.sub.3 Receptor. Bioorg. Med. Chem. Let, 1995, 5, 219) described: carboxamnidobiphenyls which have affinity at dopamine D.sub.3 receptors. The novel compounds of the present invention differ significantly from this prior art in that the two aromatic rings of the aromatic carboxamide are fused at the ortho position to create a tricyclic ring system.